Research on the gut microbiome has gained high popularity and almost every disease has meanwhile been linked to alterations in microbiome composition. Typically assessed via stool samples, the microbiome displays a huge diversity with a multitude of environmental parameters already identified as contributing to its character. Despite impressive scientific progress, normal microbiome diversity remains largely unexplained and it is tempting to speculate some of the yet unexplained variance is hidden in normal gut physiology. Although a few genome/phenome-wide associations studies have recently highlighted physiological parameters such as stool frequency,known as contributing to microbiome diversity, there is a large knowledge base from decades of basic research on gut functions that can be explored for possible links to stool features and microbiome characteristics. And, when extrapolating findings from faecal samples to the biology in the intestinal lumen or the mucosal microenvironment, gut anatomy and physiology features need to be considered. Similarly, differences in anatomy and physiology between rodents and humans need attention when discussing findings in animals in relation to human physiology and nutrition.

The gut microbiota plays crucial roles in maintaining the health and homeostasis of its host throughout lifespan, including through its ability to impact brain function and regulate behaviour during ageing. Studies have shown that there are disparate rates of biologic ageing despite equivalencies in chronologic age, including in the development of neurodegenerative diseases, which suggests that environmental factors may play an important role in determining health outcomes in ageing. Recent evidence demonstrates that the gut microbiota may be a potential novel target to ameliorate symptoms of brain ageing and promote healthy cognition. This review highlights the current knowledge around the relationships between the gut microbiota and host brain ageing, including potential contributions to age-related neurodegenerative diseases. Furthermore, we assess key areas for which gut microbiota-based strategies may present as opportunities for intervention.

The identification of functional processes taking place in microbiome communities augment traditional microbiome taxonomic studies, giving a more complete picture of interactions taking place within the community. While there are applications that perform functional annotation on metagenomes or metatranscriptomes, very few of these are able to link taxonomic identity to function or are limited by their input types or databases used. Here we present MetaFunc, a workflow which takes RNA sequences as input reads, and from these (1) identifies species present in the microbiome sample and (2) provides gene ontology annotations associated with the species identified. In addition, MetaFunc allows for host gene analysis, mapping the reads to a host genome, and separating these reads, prior to microbiome analyses. Differential abundance analysis for microbe taxonomies, and differential gene expression analysis and gene set enrichment analysis may then be carried out through the pipeline. A final correlation analysis between microbial species and host genes can also be performed. Finally, MetaFunc builds an R shiny application that allows users to view and interact with the microbiome results. In this paper, we showed how MetaFunc can be applied to metatranscriptomic datasets of colorectal cancer.

One of the fascinating outcomes of human microbiome studies adopting multi-omics technology is its ability to decipher millions of microbial encoded functions in the most complex and crowded microbial ecosystem, including the human gastrointestinal (GI) tract without cultivating the microbes. It is well established that several functions that modulate the human metabolism, nutrient assimilation, immunity, infections, disease severity and therapeutic efficacy of drugs are mostly of microbial origins. In addition, these microbial functions are dynamic and can disseminate between microbial taxa residing in the same ecosystem or other microbial ecosystems through horizontal gene transfer. For clinicians and researchers alike, understanding the toxins, virulence factors and drug resistance traits encoded by the microbes associated with the human body is of utmost importance. Nevertheless, when such traits are genetically linked with mobile genetic elements (MGEs) that make them transmissible, it creates an additional burden to public health. This review mainly focuses on the functions of gut commensals and the dynamics and crosstalk between commensal and pathogenic bacteria in the gut. Also, the review summarises the plethora of MGEs linked with virulence genes present in the genomes of various enteric bacterial pathogens, which are transmissible among other pathogens and commensals.

The 10th International Yakult Symposium was held in Milan, Italy, on 13–14 October 2022. Two keynote lectures covered the crewed journey to space and its implications for the human microbiome, and how current regulatory systems can be adapted and updated to ensure the safety of microorganisms used as probiotics or food processing ingredients. The remaining lectures were split into sections entitled “Chances” and “Challenges.” The “Chances” section explored opportunities for the science of probiotics and fermented foods to contribute to diverse areas of health such as irritable bowel syndrome, major depression, Parkinson’s disease, immune dysfunction, infant colic, intensive care, respiratory infections, and promoting healthy longevity. The “Challenges” section included selecting appropriate clinical trial participants and methodologies to minimise heterogeneity in responses, how to view probiotics in the context of One Health, adapting regulatory frameworks, and understanding how substances of bacterial origin can cross the blood–brain barrier. The symposium provided evidence from cutting-edge research that gut eubiosis is vital for human health and, like space, the microbiota deserves further exploration of its vast potential.

The gut microbiota is a dynamic ecosystem involved in multiple physiological processes that affect host health. Several factors affect intestinal microbial communities including dietary exposure to xenobiotics, which is highly concerning due to their widespread distribution. Current knowledge of this topic comes from culture-dependent methods, 16S rRNA amplicon fingerprinting, and metagenomics, but a standardised procedures framework remains lacking. This minireview integrates 45 studies from a systematic search using terms related to gut microbiota and its disruption. Only publications encompassing dietary-oral exposure and experimental gut microbiota assessments were included. The results were divided and described according to the biological model used and the disruption observed in the gut microbiota. An overall dysbiotic effect was unclear due to the variety of contaminants and hosts evaluated and the experimental gaps between publications. More standardised experimental designs, including WGS and physiological tests, are needed to establish how a particular xenobiotic can alter the gut microbiota and how the results can be extrapolated.

White kidney bean extract (WKBE) is a nutraceutical often advocated as an anti-obesity agent. The main proposed mechanism for these effects is alpha-amylase inhibition, thereby slowing carbohydrate digestion and absorption. Thus, it is possible that WKBE could impact the gut microbiota and modulate gut health. We investigated the effects of supplementing 20 healthy adults with WKBE for 1 week in a randomised, placebo-controlled crossover trial on the composition of the gut microbiota, gastrointestinal (GI) inflammation (faecal calprotectin), GI symptoms, and stool habits. We conducted in vitro experiments and used a gut model system to explore potential inhibition of alpha-amylase. We gained qualitative insight into participant experiences of using WKBE via focus groups. WKBE supplementation decreased the relative abundance of Bacteroidetes and increased that of Firmicutes, however, there were no significant differences in post-intervention gut microbiota measurements between the WKBE and control. There were no significant effects on GI inflammation or symptoms related to constipation, or stool consistency or frequency. Our in vitro and gut model system analyses showed no effects of WKBE on alpha-amylase activity. Our findings suggest that WKBE may modulate the gut microbiota in healthy adults, however, the underlying mechanism is unlikely due to active site inhibition of alpha-amylase.

The evolution of the understanding of the intestinal microbiota and its influence on our organism leverages it as a potential protagonist in therapies aimed at diseases that affect not only the intestine but also neural pathways and the central nervous system itself. This study, developed from a thorough systematic review, sought to demonstrate the influence of the intervention on the intestinal microbiota in subjects with Alzheimer’s disease. Clinical trials using different classes of probiotics have depicted noteworthy remission of symptoms, whose measurement was performed based on screenings and scores applied before, during, and after the period of probiotics use, allowing the observation of changes in functionality and symptomatology of patients. On the other hand, faecal microbiota transplantation requires further validation through clinical trials, even though it has already been reported in case studies as promising from the symptomatology point of view. The current compilation of studies made it possible to demonstrate the potential influence of the intestinal microbiota on Alzheimer’s pathology. However, new clinical studies with a larger number of participants are needed to obtain further clarification on pathophysiological correlations.

Environmental stressors can disrupt the gut–brain relationship and alter the gut microbial composition, potentially leading to chronic pain, including neuropathic pain (NP). To understand this complex relationship, we conducted a systematic scoping review to examine the gut microbial-neuroimmune connection to NP and the potential therapeutic targets. The review includes English-language manuscripts in databases such as MEDLINE, Cochrane, and DOAJ between January 2000 and April 2022. Out of the 48 full texts examined, only 15 articles met the inclusion criteria. These included a randomised controlled trial involving 327 individuals, an in vitro, and 13 animal model studies. The findings suggest that the gut flora plays a role in the immunological, neurological, and metabolic signalling pathways associated with NP. Animal studies have been the primary focus in this area, indicating that an imbalanced-gut microbiome and subsequent activation of biochemical and neuro-immunologic pathways may influence the development of NP. This review provides a comprehensive summary of the gut microbiome-immune-NP axis and identifies potential therapeutic targets. However, since most of the evidence comes from animal studies, future research should include clinical trials to gain a better understanding of the role of gut microbiota in NP and discover new therapeutic strategies.

The industrialisation of Western food systems has reduced the regular consumption of lacto-fermented vegetables (LFV). Consuming LFV may exert health benefits through the alteration of the gut microbiome, but the mechanisms involved remain unclear. To start understanding the possible benefits of LFV, we compared faecal microbial diversity and composition, as well as dietary habits between individuals who regularly consume LFV (n = 23) and those who do not (n = 24). We utilised microbial DNA amplicon sequencing (16S rRNA and ITS2) and untargeted metabolomics (LC–MS) to analyse stool samples. Study participants also provided three consecutive days of dietary data. Results show minor effects on microbiome composition; with the enrichment of a few microorganisms potentially associated with vegetable ferments, such as Leuconostoc mesenteroides and Rhodotorula mucilaginosa (P < 0.05), in LFV consumers. However, LFV consumption had greater effects on the faecal metabolome, with higher abundances of butyrate, acetate, and valerate (P < 0.05) and significantly greater metabolome diversity (P < 0.001). Overall, the observations of minor changes in the faecal microbiome and greater effects on the faecal metabolome from LFV consumption warrant further investigations on the health significance of LFV as regular components of the daily diet in humans.

Risk of bias assessment is a critical step of any meta-analysis or systematic review. Given the low sample count of many microbiome studies, especially observational or cohort studies involving human subjects, many microbiome studies have low power. This increases the importance of performing meta-analysis and systematic review for microbiome research in order to enhance the relevance and applicability of microbiome results. This work proposes a method based on the ROBINS-I tool to systematically consider sources of bias in microbiome research seeking to perform meta-analysis or systematic review for microbiome studies.

Consumption of probiotics and/or yogurt could be a solution for restoring the balance of the gut microbiota. This study examined associations of regular intake of probiotic supplements or yogurt with the gut microbiota among a diverse population of older adults (N=1,861; 60–72 years). Faecal microbial composition was obtained from 16S rRNA gene sequencing (V1–V3 region). General linear models were used to estimate the associations of probiotic supplement or yogurt intake with microbiome measures adjusting for covariates. Compared to non-yogurt consumers (N=1,023), regular yogurt consumers (≥once/week, N=818) had greater Streptococcus (β=0.29, P=0.0003) and lower Odoribacter (β=−0.33, P<0.0001) abundance. The directions of the above associations were consistent across the five ethnic groups but stronger among Japanese Americans (Streptococcus: β=0.56, P=0.0009; Odoribacter: β=−0.62, P=0.0005). Regular intake of probiotic supplements (N=175) was not associated with microbial characteristics (i.e., alpha diversity and the abundance of 152 bacteria genera). Streptococcus is one of the predominant bacteria genera in yogurt products, which may explain the positive association between yogurt consumption and Streptococcus abundance. Our analyses suggest that changes in Odoribacter were independent of changes in Streptococcus abundance. Future studies may investigate whether these microbial genera and their sub-level species mediate potential pathways between yogurt consumption and health.

Gestational diabetes mellitus (GDM) is a rising global health problem that affects approximately 6% of pregnant women. Lifestyle interventions, particularly diet, and exercise are the first-line treatment, followed by pharmacotherapy, but with associated side effects to both mother and offspring. Modulation of gut microbiota may help prevent or manage GDM. Some gut bacterial groups associated with GDM are also associated with inflammatory biomarkers and gut dysbiosis. Available literature reports that low-glycaemic index diet reduces maternal fasting and 2-hour postprandial glucose and maintains a beneficial gut bacterial composition. Pre- and probiotics can aid GDM therapy by modulating gut microbiota to eubiotic status and improving glucose metabolism. Probiotics as adjuvant GDM therapy should consider bacterial strains, dosage, and treatment duration. Limitations in their use require further studies to develop specific probiotic-based GDM supplement therapy that impacts glycaemic control and inflammatory status by reducing fasting plasma glucose, insulin resistance, and improving lipid profiles of pregnant women.

Research on the gut microbiome and mental health among children and adolescents is growing. This umbrella review provides a high-level overview of current evidence syntheses to amalgamate current research and inform future directions. Searches were conducted across seven databases for peer-reviewed pediatric (<18 years) review literature. Studies reporting gut microbiome composition and/or biotic supplementation on depression, bipolar disorder, anxiety, attention deficit hyperactivity disorder, autism spectrum disorder (ASD), or obsessive-compulsive disorder (OCD) were included. Deduplication and screening took place in Covidence. A sensitivity analysis was conducted to assess the degree of primary study overlap. Among the 39 included review studies, 23 (59%) were observational and 16 (41%) were interventional. Most reviews (92%) focused on ASD. Over half (56%) of the observational and interventional reviews scored low or critically low for methodological quality. A higher abundance of Clostridium clusters and a lower abundance of Bifidobacterium were consistently observed in ASD studies. Biotic supplementation was associated with ASD symptom improvement. Gut microbiome-mental health evidence syntheses in child and youth depression, anxiety, bipolar disorder, and OCD are lacking. Preliminary evidence suggests an association between specific microbiota and ASD symptoms, with some evidence supporting a role for probiotic supplementation ASD therapy.

Ulcerative colitis (UC) is an immune-mediated inflammation of the colonic mucosa. Gut microbiota dysbiosis may play a significant role in disease pathogenesis by causing shifts in metabolomic profiles within the gut. To identify differences and trends in the metabolomic profile of paediatric UC patients pre- and post-faecal microbiota transplants (FMT). Forty-six paediatric patients with mild-to-moderate UC and 30 healthy paediatric patients were enrolled in this study. Baseline stool samples were collected prior to FMT initiation and at months 1, 3, 6, and 12 post-FMT. Pediatric Ulcerative Colitis Activity Index (PUCAI) scores were calculated at baseline and months 1, 3, 6, and 12 after FMT. The average Bray–Curtis dissimilarities to healthy subjects decreased after FMT. In principal coordinate analysis plots, UC patients’ centroids drew nearer to healthy individuals. The variance explained by phenotype (Healthy versus UC) reduced and remained significant. From 1 to 3 months after FMT, PUCAI trends were statistically significant and decreasing. PUCAI scores remain flat starting 6 months after FMT. This study concludes that paediatric UC patients have a significantly different baseline metabolite profile than healthy controls. Although being time limited, FMT significantly altered these metabolite profiles and shifted them towards that of healthy controls.